A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma
Overview
- Phase
- Early Phase 1
- Intervention
- Troriluzole
- Conditions
- Glioblastoma
- Sponsor
- Ugonma Chukwueke
- Enrollment
- 27
- Locations
- 3
- Primary Endpoint
- The effect of troriluzole on high-gamma band power (a measure of neuronal activity) via electrocorticography during surgical resection
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This research study is studying troriluzole as a possible treatment for recurrent glioblastoma.
The name of the study drug involved in this research study is:
-Troriluzole (a tripeptide prodrug of riluzole)
Detailed Description
This is an open-label, randomized window-of-opportunity study of Troriluzole in participants with surgically accessible, recurrent isocitrate dehydrogenase wild-type (IDH WT) glioblastoma (GBM). Surgical window-of-opportunity clinical trials test how active the investigational drug is on tumors. "Investigational" means that the drug is being studied. Participants will be randomized using a 2:1 ratio into one of two study treatment groups: Group A versus Group B. Randomization means a participant is placed into a study group by chance. Group A will receive Troriluzole prior to and after standard-of-care tumor resection surgery, while Group B will not receive Troriluzole prior to standard-of-care tumor resection surgery but will receive Troluzole after surgery. The research study procedures include screening for eligibility, study treatment visits, blood tests, tumor biopsies, Magnetic Resonance Imaging (MRI) scans, and electrocardiograms (ECGs). It is expected that about 27 participants will take part in this research study Biohaven Pharmaceuticals is funding this research study by providing study drug.
Investigators
Ugonma Chukwueke
Sponsor Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years
- •Histopathologically confirmed IDH-wildtype glioblastoma, WHO Grade 4, and variants including gliosarcoma as per WHO 2021 criteria (38).
- •Prior treatment with radiotherapy with or without chemotherapy.
- •Recurrent or progressive disease with no more than 2 prior relapses.
- •Confirmed measurable disease per RANO 2.0 for GBM.
- •Tumor is documented as IDH1/2 wildtype by direct DNA sequencing, provided that it is performed in a CLIA/CAP-certified laboratory.
- •Availability of archival formalin fixed paraffin-embedded (FFPE) tumor tissue block or 20 unstained FFPE slides (5 μm thick) from any prior surgery for mutation testing and additional sequencing.
- •Karnofsky Performance Status of ≥
- •Candidate for surgical resection.
- •Tumor tissue extending to cortical gray matter based on MRI.
Exclusion Criteria
- •Laboratory values at the Screening Visit:
- •ANC count \< 1,500/mm3; growth-factor support within 7 days for filgrastim or other short acting biosimilars or 21 days for pegfilgrastim or other long acting biosimilars to increase the ANC is not allowed.
- •Platelets \<100,000/mm3;
- •Hemoglobin \< 9 g/dL;
- •Total bilirubin \> 2 × the upper limit of normal (ULN) (unless subject has documented history of Gilbert's Syndrome in which case subject may be enrolled if total bilirubin is less than 5 mg/dL, assuming all other criteria are fulfilled);
- •Aspartate aminotransferase (AST \[SGOT\]) \> 1.5 x ULN;
- •Alanine aminotransferase (ALT \[SGPT\]) \> 1.5 x ULN;
- •Serum creatinine \> 1.5 mg/dL or a calculated creatinine clearance \< 60 mL/min; and
- •Positive serum β-hCG test in any individual assigned female at birth and is of childbearing potential (defined as ≤ 50 years of age, or \> 50 years of age with a history of amenorrhea for ≤12 months prior to study entry).
- •Has presence of diffuse leptomeningeal disease or extracranial disease.
Arms & Interventions
Group A: Presurgical Troriluzole
18 participants will be randomly assigned to this group and with complete: * Baseline visit with assessments and MRI. * Cycle 0: * Day -6 through Day 0: Predetermined dose of Troriluzole 2x daily. * Day 0: pre-op MRI * Day 0: standard of care surgical resection of tumor * Day 0: post-op MRI * Cycle 1 through Cycle 3: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * Cycle 3 through End of Treatment: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * MRIs every 8 weeks while on treatment. * End of study visit with MRI * Follow up every 3 months for 1 year, and then every 6 months for the next 3 years.
Intervention: Troriluzole
Group B: Surgery + Troriluzole
9 participants will be randomly assigned to this group and with complete: * Baseline visit with assessments and MRI * Day 0: pre-op MRI * Day 0: standard of care surgical resection of tumor * Day 0: post-op MRI * Cycle 1 through Cycle 3: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * Cycle 3 through End of Treatment: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * MRIs every 8 weeks while on treatment. * End of study visit with MRI * Follow up every 3 months for 1 year, and then every 6 months for the next 3 years.
Intervention: Troriluzole
Outcomes
Primary Outcomes
The effect of troriluzole on high-gamma band power (a measure of neuronal activity) via electrocorticography during surgical resection
Time Frame: At time of surgery
Data will be summarized using descriptive statistics to compare between participants who received presurgical troriluzole and who did not
Secondary Outcomes
- Grade 3-5 Treatment Related Adverse Event(From tumor tissue resected at surgery)
- Concentrations of Extracellular Glutamate in Resected Tissue by MALDI-MSI(From tumor tissue resected at surgery)
- Proliferation Rate (Ki-67) in Resected Tissue(From tumor tissue resected at surgery)
- Protein Levels of NLGN3 in Resected Tissue(From tumor tissue resected at surgery)
- Protein Levels of Phosphorylated AMPA Receptor Subunits (e.g. GluA2) in Resected Tissue(From tumor tissue resected at surgery)
- Tumor Tissue Concentration of Troriluzole by MALDI-MSI(From tumor tissue resected at surgery)